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Cited by 12Protein Kinase Regulation and GTPase SignalingMitochondrial Function and PathologyCellular transport and secretion

Breaking up is hard to do: RalA, mitochondrial fission and cancer

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Kashatus, David F., Counter, Christopher M.·2011·Small GTPases
DOI 10.4161/sgtp.18284PMC PMC3337163
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Abstract

The small GTPases RalA and RalB are activated downstream of oncogenic Ras. While activation of RalA is critically important for tumor initiation and growth of Ras-driven cancers, the highly similar small GTPase RalB is implicated in cell survival and metastasis. This difference in function between these two related proteins maps to the C-terminus, a 30 amino acid region that regulates subcellular localization and contains several potential phosphorylation sites. Here we discuss our recent evidence that phosphorylation by the mitotic kinase Aurora A promotes RalA relocalization to mitochondrial membranes, where it recruits the effector RalBP1 and the large dynamin-related GTPase Drp1 to promote mitochondrial fission. As upregulation of both RalA and Aurora A have been observed in human tumors, and phosphorylation of RalA at the site targeted by Aurora A promotes tumorigenesis, it is possible that regulation of mitochondrial fission is one mechanism by which RalA promotes cancer.

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Cited by

Sorted by citations

Authors
Kashatus, D. F., & Counter, C. M.
Affiliations
Duke University (US)
Corresponding author
Counter, Christopher M.
ORCID
Venue
Small GTPases
Publisher
Informa UK Limited
Published
2011-11
Volume
2
Issue
6
Pages
329-333
ISSN
  • 2154-1248 (ISSN-L)
  • 2154-1256
DOI
10.4161/sgtp.18284
PMC
PMC3337163
OpenAlex
W2080864517
Cited by
12
References
3
Citations by year
2024: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 2
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Small GTPases (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Leukemia and Lymphoma Society
  • National Institutes of Health
  • National Cancer Institute (R01CA094184)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
RalA, RalB, oncogenic Ras, AURKA, phosphorylation, C-terminal regulatory domain, mitochondrial fission, Drp1, RALBP1, carcinogenesis, metastasis, cell survival

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